Topical PrEP Comparison: Tenofovir Alone May Be as Effective as Tenofovir/FTC, Study Finds

My name is Dr. Walid Heneine. I work at the U.S. Centers for Disease Control and Prevention [CDC] in the Division of HIV/AIDS Prevention. Thank you very much for having me today to speak about our work related to topical prophylaxis with gels containing antiretroviral drugs.

Pre-exposure prophylaxis, or PrEP, is one of the most promising areas of HIV prevention and research. [There] are several trials that are now evaluating PrEP either taken orally or topically through gels. These trials are currently underway around the world; they will give us some first answers on the efficacy and safety of PrEP, [including] how well they can prevent HIV transmission.

Walid Heneine, Ph.D.

However, animal studies like the one that we are discussing today are a critical part of the preparations for the next generation of PrEP research. Our study compares the effectiveness of a topical gel containing one drug, tenofovir [TDF, Viread], with another gel containing a combination of two drugs, tenofovir and FTC [emtricitabine, Emtriva].¹ We looked at the effectiveness of these two gels in a monkey model against vaginal transmission of the simian form of HIV.

When applied 30 minutes before challenge with [i.e., exposure to] the virus, we found that both gels completely protected against vaginal transmission, suggesting that you can achieve a very high level of protection with gels containing single drugs.

Obviously, this was somewhat of a surprising result. Previous animal studies that we have done with oral PrEP all suggested that drug combinations are more effective than single drugs, so this is the first instance in which we're seeing that you can achieve a high level of protection by topically applying gel that contains a single drug.

This is very promising. We are awaiting right now the human data from these gel studies, so that we can see how well the human data correlates with the monkey data. All this work we are doing right now will help us prepare for the next PrEP trial research.

How do you explain the difference compared to previous studies, in which they seemed to show that it was absolutely better to use a combination drug?

We think it has to do with the amount of drug that the gel delivers to the point of entry for the virus -- vaginal tissues, in this case. We think that the concentration of the tenofovir in the gel is much higher than when you take tenofovir orally, so you have higher levels of drug where the virus enters from applying the gel topically versus when you are taking a pill orally. That's the possible explanation. We are now generating drug-level data [in which we] follow oral dosing of the pill compared to topical application with the gel to further explain those findings.

What's the consistency of this gel?

This is like a normal gel that you could use like for lubrication: It's viscous, clear, odorless. It has a good consistency.

It's similar to other microbicides being developed?

It's similar to other microbicides. However, the active ingredient in them is now antiretroviral drugs. This is the new generation of microbicide gels that use new classes of active components, namely these antiretroviral drugs.

Did you see any adverse effects?

No. We did acute toxicity studies, drug-level studies and so forth. At least in the monkeys, we have not seen any adverse effect. Clearly, all these products, particularly 1% tenofovir, are now in safety studies in humans -- for vaginal application as well as for rectal application.

Thank you very much.

Thank you for having me.

This transcript has been edited lightly for clarity.

Reference

1. Heneine W, Dobard C, Parikh U, et al. Complete Protection against Repeated Vaginal Simian HIV Exposures in Macaques by a Topical Gel Containing Tenofovir Alone or with Emtricitabine. In: Program and abstracts of the 16th Conference on Retroviruses and Opportunistic Infections; February 8-11, 2009; Montréal, Canada. Abstract 46.